JP2015525237A5 - - Google Patents

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JP2015525237A5
JP2015525237A5 JP2015518318A JP2015518318A JP2015525237A5 JP 2015525237 A5 JP2015525237 A5 JP 2015525237A5 JP 2015518318 A JP2015518318 A JP 2015518318A JP 2015518318 A JP2015518318 A JP 2015518318A JP 2015525237 A5 JP2015525237 A5 JP 2015525237A5
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本発明の最も好ましい実現形態として、本発明の組成物は、下記から選択されるアミノ酸配列を含む変形されたＴＮＦＲＩまたは変形されたＴＮＦＲＩ切片の１種以上を有効成分として含有する：
配列番号１に記載された天然型ＴＮＦＲＩのアミノ酸配列（ＴＮＦＲＩ）でＬ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ｇ／Ｋ１６１Ｎ、または、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｄ２０７Ｎであるアミノ酸変形を含むアミノ酸配列；
配列番号１に記載された天然型ＴＮＦＲＩのアミノ酸配列の４１番〜２１１番からなるアミノ酸配列（ＴＮＦＲＩ１７１）でＬ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ｇ／Ｋ１６１Ｎ、または、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｄ２０７Ｎであるアミノ酸変形を含むアミノ酸配列；または
配列番号１に記載された天然型ＴＮＦＲＩのアミノ酸配列の４１番〜１６６番からなるアミノ酸配列（ＴＮＦＲＩ１２６）でＬ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ｇ／Ｋ１６１Ｎであるアミノ酸変形を含むアミノ酸配列。
As the most preferred mode of realization of the present invention, the composition of the present invention contains as an active ingredient one or more of a modified TNFRI or a modified TNFRI section comprising an amino acid sequence selected from:
Amino acid sequence comprising the amino acid sequence of L68V / S92M / H95F / R97P / H98G / K161N or L68V / S92M / H95F / R97P / H98A / D207N in the amino acid sequence (TNFRI) of natural TNFRI set forth in SEQ ID NO: 1 ;
L68V / S92M / H95F / R97P / H98G / K161N , or L68V / S92M / H95F / R97P / H98A in the amino acid sequence (TNFRI171) consisting of amino acids 41 to 211 of the amino acid sequence of natural TNFRI described in SEQ ID NO: 1. An amino acid sequence comprising an amino acid variant that is / D207N; or an amino acid sequence consisting of amino acids 41 to 166 of the natural TNFRI described in SEQ ID NO: 1 (TNFRI126), L68V / S92M / H95F / R97P / H98G / K161N An amino acid sequence comprising an amino acid variant that is

Claims (11)

配列番号１に記載された天然型ＴＮＦＲＩのアミノ酸配列（ＴＮＦＲＩ）で、
ｉ）Ｌ６８Ｖ／Ｓ９２Ｉ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｋ１６１Ｎ、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｄ２０７Ｎ、または、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ｇ／Ｋ１６１Ｎ中から選択されるアミノ酸変形を含むアミノ酸配列；
ｉｉ）配列番号１に記載された天然型ＴＮＦＲＩのアミノ酸配列の４１番〜２１１番からなるアミノ酸配列（ＴＮＦＲＩ１７１）でＬ６８Ｖ／Ｓ９２Ｉ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｋ１６１Ｎ、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｄ２０７Ｎ、または、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ｇ／Ｋ１６１Ｎ中から選択されるアミノ酸変形を含むアミノ酸配列；
ｉｉｉ）配列番号１に記載された天然型ＴＮＦＲＩのアミノ酸配列の４１番〜１６６番からなるアミノ酸配列（ＴＮＦＲＩ１２６）でＬ６８Ｖ／Ｓ９２Ｉ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｋ１６１Ｎ、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｄ２０７Ｎ、または、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ｇ／Ｋ１６１Ｎ中から選択されるアミノ酸変形を含むアミノ酸配列；及び
ｉｖ）配列番号１に記載された天然型ＴＮＦＲＩのアミノ酸配列の４１番〜１４５番からなるアミノ酸配列（ＴＮＦＲＩ１０５）でＬ６８Ｖ／Ｓ９２Ｉ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｋ１６１Ｎ、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｄ２０７Ｎ、または、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ｇ／Ｋ１６１Ｎ中から選択されるアミノ酸変形を含むアミノ酸配列
からなる群から選択されるアミノ酸配列を含む変形されたＴＮＦＲＩの１種以上を含むことを特徴とする眼球乾燥症の予防または治療用組成物。 The amino acid sequence of natural TNFRI described in SEQ ID NO: 1 (TNFRI),
i) Amino acid sequence comprising an amino acid variant selected from L68V / S92I / H95F / R97P / H98A / K161N, L68V / S92M / H95F / R97P / H98A / D207N, or L68V / S92M / H95F / R97P / H98G / K161N ;
ii) L68V / S92I / H95F / R97P / H98A / K161N, L68V / S92M / H95F / R97P / H98A in the amino acid sequence (TNFRI171) consisting of amino acids 41 to 211 of the amino acid sequence of natural TNFRI described in SEQ ID NO: 1 Amino acid sequence comprising an amino acid variant selected from / D207N or L68V / S92M / H95F / R97P / H98G / K161N ;
iii) L68V / S92I / H95F / R97P / H98A / K161N, L68V / S92M / H95F / R97P / H98A in the amino acid sequence (TNFRI126) consisting of amino acids 41 to 166 of the natural TNFRI described in SEQ ID NO: 1 / D207N or the amino acid sequence comprises an amino acid modification selected from among L68V / S92M / H95F / R97P / H98G / K161N,; and
iv) L68V / S92I / H95F / R97P / H98A / K161N, L68V / S92M / H95F / R97P / H98A in the amino acid sequence (TNFRI105) consisting of amino acids 41 to 145 of the amino acid sequence of natural TNFRI described in SEQ ID NO: 1 / D207N, or a modified TNFR I comprising an amino acid sequence selected from the group consisting of amino acid sequences comprising an amino acid variation selected from L68V / S92M / H95F / R97P / H98G / K161N a composition for preventing or treating ocular bulb xerosis you comprising more. 配列番号１に記載された天然型ＴＮＦＲＩのアミノ酸配列（ＴＮＦＲＩ）で
ｉ）Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ｇ／Ｋ１６１Ｎ、または、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｄ２０７Ｎであるアミノ酸変形を含むアミノ酸配列；及び
ｉｉ）配列番号１に記載された天然型ＴＮＦＲＩのアミノ酸配列の４１番〜２１１番からなるアミノ酸配列（ＴＮＦＲＩ１７１）でＬ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ｇ／Ｋ１６１Ｎ、または、Ｌ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ａ／Ｄ２０７Ｎであるアミノ酸変形を含むアミノ酸配列
からなる群から選択されるアミノ酸配列を含む変形されたＴＮＦＲＩの１種以上を含むことを特徴とする請求項１に記載の眼球乾燥症の予防または治療用組成物。 I) L68V / S92M / H95F / R97P / H98G / K161N or L68V / S92M / H95F / R97P / H98A / D207N in the amino acid sequence of natural TNFRI described in SEQ ID NO: 1 (TNFRI) Amino acid sequence; and ii) L68V / S92M / H95F / R97P / H98G / K161N or L68V / S92M which is an amino acid sequence (TNFRI171) consisting of amino acids 41 to 211 of the amino acid sequence of natural TNFRI described in SEQ ID NO: 1 The eyeball of claim 1 , comprising one or more modified TNFR I comprising an amino acid sequence selected from the group consisting of amino acid sequences comprising an amino acid sequence comprising / A95F / R97P / H98A / D207N Prevention or treatment of dryness Composition. 配列番号１８又は２０から選択されるアミノ酸配列を含む変形されたＴＮＦＲＩの１種以上を含むことを特徴とする請求項１に記載の眼球乾燥症の予防または治療用組成物。 The composition for prevention or treatment of xerophthalmia according to claim 1 , comprising one or more modified TNFR I comprising an amino acid sequence selected from SEQ ID NO: 18 or 20 . 前記変形されたＴＮＦＲＩは、大腸菌発現系での産生のための変形がさらに含まれたことを特徴とする請求項１から３のいずれかに記載の眼球乾燥症の予防または治療用組成物。 The composition for preventing or treating xerophthalmia according to any one of claims 1 to 3 , wherein the modified TNFR I further includes a modification for production in an E. coli expression system. 大腸菌発現系での産生のための変形は、アミノ酸配列のアミノ末端に信号配列またはメチオニン（Ｍｅｔ）が付加されたことを特徴とする請求項４に記載の眼球乾燥症の予防または治療用組成物。 5. The composition for prevention or treatment of xerophthalmia according to claim 4 , wherein a signal sequence or methionine (Met) is added to the amino terminus of the amino acid sequence as a modification for production in an E. coli expression system. . 請求項１から３のいずれかに記載の変形されたＴＮＦＲＩの二つ以上が共有結合によって連結された形態の変形されたＴＮＦＲＩ複合体１種以上を含む眼球乾燥症の予防または治療用組成物。 Modified two or more compositions for the prevention or treatment of xerophthalmia containing more than TNFR I double coalesce one member deformation of the connecting form by covalent attachment of TNFR I according to any one of claims 1 to 3 object. 前記変形されたＴＮＦＲＩは、糖化、アシル化、メチル化、リン酸化、ハシル化、カルバミル化、硫酸化、プレニル化、酸化、グアニジル化、アミジン化、カルバミル化、トリニトロフェニル化、硝酸化、またはペグ化されていることを特徴とする請求項１から３のいずれかに記載の眼球乾燥症の予防または治療用組成物。 The modified TNFR I is saccharified, acylated, methylated, phosphorylated, hasilated, carbamylated, sulfated, prenylated, oxidized, guanidylated, amidated, carbamylated, trinitrophenylated, nitrated, The composition for prevention or treatment of xerophthalmia according to any one of claims 1 to 3 , wherein the composition is pegylated. 請求項１から３のいずれかに記載の変形されたＴＮＦＲＩを暗号化する遺伝子を含む眼球乾燥症の予防または治療用組成物。 A composition for the prevention or treatment of xerophthalmia, comprising a gene encoding the modified TNFR I according to any one of claims 1 to 3 . 請求項１から３のいずれかに記載の組成物を含む局所点眼用製剤。 A topical ophthalmic preparation comprising the composition according to any one of claims 1 to 3 . 点眼剤または眼軟膏であることを特徴とする請求項９に記載の局所点眼用製剤。 The topical eye drop preparation according to claim 9 , which is an eye drop or an eye ointment. 変形されたＴＮＦＲＩを含む眼球乾燥症の予防または治療用組成物であって、前記の変形されたＴＮＦＲＩが、配列番号１に記載された天然型ＴＮＦＲＩのアミノ酸配列の４１番〜２１１番からなるアミノ酸配列（ＴＮＦＲＩ１７１）でＬ６８Ｖ／Ｓ９２Ｍ／Ｈ９５Ｆ／Ｒ９７Ｐ／Ｈ９８Ｇ／Ｋ１６１Ｎであるアミノ酸変形を含むアミノ酸配列を含む前記組成物。A composition for preventing or treating xerophthalmia comprising a modified TNFRI, wherein the modified TNFRI comprises amino acids 41 to 211 of the amino acid sequence of the natural TNFRI set forth in SEQ ID NO: 1. Said composition comprising an amino acid sequence comprising an amino acid variant with the sequence (TNFRI171) being L68V / S92M / H95F / R97P / H98G / K161N.
JP2015518318A 2012-06-21 2013-02-07 Novel uses of modified human tumor necrosis factor receptor-1 polypeptide Active JP6087429B2 (en)

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EP3288379B1 (en) 2015-05-01 2021-11-03 Onl Therapeutics, Inc. Peptide compositions and methods of use
US20190177407A1 (en) * 2016-06-20 2019-06-13 Novartis Ag Methods of treating dry eye disease using tnf alpha antagonists
CA3207852A1 (en) 2021-01-14 2022-07-21 Hanall Biopharma Co., Ltd. A stable ophthalmic composition comprising tanfanercept, which is free of stabilizer or substantially free of stabilizer
WO2022154142A1 (en) * 2021-01-14 2022-07-21 주식회사한올바이오파마 Treatment of dry eye syndrome using tanfanercept ophthalmic composition

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WO2000027421A2 (en) 1998-11-06 2000-05-18 The Schepens Eye Research Institute, Inc. LOCAL USE OF SOLUBLE TUMOR NECROSIS RECEPTOR I (sTNFRI) FOR PROPHYLAXIS AND TREATMENT OF CORNEAL TRANSPLANT REJECTION AND OTHER DISORDERS OF THE EYE
US6177077B1 (en) 1999-02-24 2001-01-23 Edward L. Tobinick TNT inhibitors for the treatment of neurological disorders
US6379666B1 (en) 1999-02-24 2002-04-30 Edward L. Tobinick TNF inhibitors for the treatment of neurological, retinal and muscular disorders
US6204270B1 (en) 1999-11-12 2001-03-20 Eyal S. Ron Ophthalmic and mucosal preparations
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CN101591388A (en) 2008-05-30 2009-12-02 上海复旦张江生物医药股份有限公司 A kind of soluble TNF acceptor mutant
JP5746191B2 (en) 2009-10-19 2015-07-08 ハナル バイオファーマ カンパニーリミテッドＨａｎＡｌｌ Ｂｉｏｐｈａｒｍａ Ｃｏ．， Ｌｔｄ． Modified human tumor necrosis factor receptor-1 polypeptide or fragment thereof and method for producing the same
KR101273893B1 (en) * 2010-09-13 2013-06-14 한올바이오파마주식회사 Modified human tumor necrosis factor receptor-1 polypeptides or fragments thereof and method for preparing the same
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